Hyperoxygenation During CPB: When Should We Use It?

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Hyperoxygenation During CPB When Should We Use
It?

• Gary Grist RN CCP, Chief PerfusionistThe
  Childrens Mercy Hospitals and ClinicsKansas
  City, Missouriggrist_at_cmh.eduNo Disclosures

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Some consider it a fact that use of hyperoxia on
cardiopulmonary bypass (CPB) has negative effects
on patient outcome by increasing the danger of
oxygen toxicity or reperfusion injury. This
belief has become a 'sacred cow' among many
perfusionists. However, the manipulation of
oxygen on CPB can be used to the patient's
benefit. It is incumbent upon the perfusionist
to understand the need for the manipulation of
oxygen concentration and master the techniques
needed to provide the patient with the greatest
benefit. A 'one size fits all' approach to
oxygenation strategy, be it normoxia, hyperoxia,
or something in between can rob the patient of
the benefits that the free range of oxygen
manipulation, from high to low, can provide.
Oxygen Pressure Field Theory conceptualizes the
manipulation of oxygen concentration such that
the perfusionist can understand the mechanics of
microvascular gas exchange. Hyperoxia can be
beneficial in one situation and detrimental in
another as can normoxia. This presentation
discusses oxygen manipulation in six clinical
situations. 1. Nitrogen entrainment Special
equipment has shown that gaseous microemboli
(GME) may occur in the cerebral circulation of
any patient on CPB. The GME are most numerous
during interventions by perfusionists and were
associated with the worst neuropsychological
outcomes. Most bubbles that enter the CPB circuit
are initially composed of room air approximately
70 nitrogen, 19 oxygen, 5 carbon dioxide and
6 water vapor. GMEs of this composition are
likely to occlude small arteries and capillaries
and cause tissue ischemia. During the periods of
high risk for GME generation and by using Boyles
Law, the perfusionist can change these bubbles to
approximately 0 nitrogen, 89 oxygen, 5 carbon
dioxide and 6 water vapor. This GME composition
is much less likely to result in capillary
occlusion. 2. Hemodilution The reduced oxygen
delivery common during CPB as a result of
hemodilution can be counter-acted to a limited
degree by the use of hyperoxia. Hyperoxia is
commonly used for humans in major, non-cardiac
surgery and has shown to 1) be safe during
anesthesia with no adverse side effects, 2)
reduce the need for blood transfusion, 3)
preserve myocardial oxygenation during low
hematocrit, 4) reverse anemic hypoxic ECG
changes, 5) increase sub-endocardial oxygen
delivery, 6) reverse non-cardiac tissue hypoxia
caused by anemia and 7) reduce the risk of wound
infection. 3. Metabolic acidosis Increases in
base deficient caused by suboptimal perfusion
(shock) can be significantly reduced using
various degrees of hyperoxia. 4. Deep
hypothermic circulatory arrest (DHCA) Hyperoxia
can be used prior to DHCA to 'oxygen load'
tissues. This can extend the period of safe
circulatory arrest before anaerobic metabolism
begins by approximately 20 minutes. 5. Oxygen
toxicity Oxygen toxicity is frequently confused
with reperfusion injury, but it occurs when
circulation is good, there is no acidosis, and
the antioxidants are functioning properly.
However, the amount of oxygen present in the
tissues overwhelms the antioxidants' ability to
neutralize reactive oxygen species. The
perfusionist who is aware of the circumstances
during which oxygen toxicity occurs can take the
proper precautions with oxygen manipulation to
prevent tissue damage. 6. Reperfusion injury
Reperfusion injury is frequently confused with
oxygen toxicity, but it occurs when circulation
is poor and acidosis is present which deactivates
the antioxidants. Reperfusion injury can occur
even during low oxygen concentration and can be
caused iatrogenically by the perfusionist. The
perfusionist can prevent tissue damage when there
is reperfusion injury potential (RIP) and he/she
can prevent damage by not allowing RIP to
develop in both instances using oxygen
manipulation.
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OBJECTIVES

• To briefly describe the oxygen pressure field
  theory and discuss scenarios where oxygen
  manipulation on cardiopulmonary bypass may be
  helpful to improve patient outcomes.
• Six situations for oxygen manipulation
• Nitrogen entrainment
• Hemodilution
• Metabolic acidosis
• Hypothermic arrest
• Oxygen toxicity
• Reperfusion injury

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1. NITROGEN ENTRAINMENT

• CNS complications from CPB
• stroke 1.5 (CABG) to 10 (valves)
• asymptomatic brain infarct by MRI 18
• Floyd et al. 2006
• Gerriets et al. 2010
• Sources of emboli
• atheroemboli from aortic manipulation
• thromboemboli
• bubbles of air
• Raymond et al. 2001

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1. NITROGEN ENTRAINMENTBrain Emboli
Cardiopulmonary Bypass Principles Practice,
Gravlee et al, Ed., 1993, pg 549
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1. NITROGEN ENTRAINMENTAir bubbles in the venous
return line Wang S, Undar A . Vacuum-assisted
venous drainage and gaseous microemboli in
cardiopulmonary bypass.J Extra Corpor Technol.
2008 Dec40(4)249-56.
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1. NITROGEN ENTRAINMENTBlood emulsification with
air by the vent and suckersMaking bloody
meringue!
Ashby MF. The properties of foams and lattices.
Philos Transact A Math Phys Eng Sci. 2006 Jan
15364(1838)15-30. Cheng KT. Air-filled,
cross-linked, human serum albumin microcapsules.
Molecular Imaging and Contrast Agent Database
(MICAD) Internet. Bethesda (MD) National
Center for Biotechnology Information (US)
2004-2010. 2006 Jul 06 updated 2008 May 08.
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1. NITROGEN ENTRAINMENTBorger MA, Feindel CM.
Cerebral emboli during cardiopulmonary bypass
effect of perfusionist interventions and aortic
cannulas. J Extra Corpor Technol 2002
34(1)29-33.
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1. NITROGEN ENTRAINMENTDealing with bubbles

• Use an arterial filter/bubble trap w/ purge
• CO2 flush the surgical field
• Add volume to the venous reservoir
• Slow down the suckers and vent
• Limit perfusionist interventions
• Use a circuit or MCA Doppler
• Ask the surgeon to stop what he is doing and fix
  the bubble source
• Increase sweep FiO2

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1. NITROGEN ENTRAINMENTConverting N2 bubbles in
blood to O2 bubblesVann RD, Butler FK, Mitchell
SJ, Moon RE.Decompression illness. Lancet. 2011
Jan 8377(9760)153-64.
Pre- oxygenator bubble Post- oxygenator bubble Post-oxygenator bubble
Gas in the bubble FiO2 21 FiO2 40 FiO2 100
N2 70 54 0
O2 19 35 89
CO2 5 5 5
H2O 6 6 6
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Understanding The Oxygen Pressure Field Krogh
Cylinder Model
Capillary radius r 5µ Capillary X-section A
? r 2 78. 5 µ2 Cylinder radius R
10 Cylinder X-section A ? R2 314 µ2
Capillary X-section Cylinder X-section
Ratio
1/4
Highest ptO2 79 mmHg
Lowest ptO2 1 mmHg
OPF Range 79 1 mmHg
R
r
Blood Flow
paO2 80 mmHg
pvO2 40 mmHg
Avg. ptO2 20 mmHg
Avg. ptO2 10 mmHg
O2 radial vectors
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PERFUSED CAPILLARY DENSITY (PCD)
R
R
Low PCD Single capillary unit
High PCD Multiple capillary units
Closed capillary unit
Increasing PCD

• WORKING MUSCLE

RESTING MUSCLE
NORMAL ORGAN FUNCTION
ORGAN SHOCK
Decreasing PCD
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Capillary radius r 5µ Capillary X-section A
? r 2 78. 5 µ2 Cylinder radius R
20 Cylinder X-section A ? R2 1256 µ2
Ratio
Capillary X-section Cylinder X-section
1/16
Anoxic tissue
1 mmHg pO2 line
ANOXIC LETHAL CORNER
R
Highest tissue pO2 79mmHg
r
Blood Flow
paO2 80mmHg
pvO2 40 mmHg
ANOXIC LETHAL CORNER
1 mmHg pO2 line
O2 radial vectors
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2. HEMODILUTIONShould Perfusionists Use A
Transfusion TriggerOn Cardiopulmonary Bypass?

• Patients with 25 Hct 2 mortality.
• Patients with 19 Hct 4 mortality.
• DeFoe et al. 2001.
• Should 19 be a trigger point?
• Reduce the mortality from 4 to 2
• NNT Transfuse 90/100 low hematocrit patients
• 2 additional patients survive
• 88 patients unnecessarily transfused
• Grist G. AmSECT Today 2009.

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2. HEMODILUTIONCounter-acting Hemodilution With
Hyperoxia

• Hyperoxia use in non-cardiac surgery
• Safe
• No adverse side effects (human experience)
• Habler et al. 2002
• Reduces the need for transfusion
• Less allogenic blood given (human experience)
• Kemming et al. 2003
• Preserves myocardial oxygenation during low
  hematocrit
• Reverses anemic hypoxic ECG changes (human
  experience)
• Increases sub-endocardial O2-delivery 24 (animal
  study)
• Kemming et al. 2004
• Reverses tissue hypoxia at low hematocrit
• Tissue pO2 increases from 10 to 18 mmHg (animal
  study)
• Meier et al. 2004
• Reduces risk of wound infection
• Supplemental O2 (80 vs 30) reduces infections
  by 39 (human experience)
• Brasel et al. 2005

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2. HEMODILUTION Formation Of An Anoxic Lethal
Corner Due To Low Hematocrit
O2 Axial Vectors
1 mmHg tissue pO2 line
Low Hct
paO2 150 mmHg
Anoxic Tissues Lethal Corner Forms
O2 Radial Vectors
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2. HEMODILUTION Augmented Axial Vectors
(Hyperoxia) Redistributes O2 To Prevent An Anoxic
Lethal Corner
Potential Lethal Corner Line
Augmented O2 Axial Vectors
Low Hct
paO2 400 mmHg
Tissues Oxygenated Lethal Corner Obliterated
Augmented O2 Radial Vectors
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3. METABOLIC ACIDOSISPoor perfusion decreased
perfused capillary density (PCD)causing tissue
anoxia
R
R
Low PCD Single capillary unit
High PCD Multiple capillary units
Increasing PCD
Closed capillary unit

• WORKING MUSCLE

RESTING MUSCLE
NORMAL ORGAN FUNCTION
SHOCK
Decreasing PCD
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3. METABOLIC ACIDOSISNormal Capillary
Configuration
Lowest tissue pO2 1mmHg
Highest tissue pO2 99mmHg
paO2 100mmHg SAO2 99
pvO2 40 mmHg SVO2 75
Blood Flow
pvCO2 45 mmHg
paCO2 40 mmHg
Lowest tissue pCO2 42mmHg
Highest tissue pCO2 47mmHg
O2 radial vectors
CO2 radial vectors
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3. METABOLIC ACIDOSISCapillary Configuration In
The Shock Patient
paO2 100mmHg SAO2 99
pvO2 40 mmHg SVO2 75
Blood Flow
pvCO2 60 mmHg
paCO2 40 mmHg
Anoxic /or Hypercapnic Lethal Corner
O2 radial vectors
CO2 radial vectors
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3. METABOLIC ACIDOSIS Poor Perfusion Decreased
Perfused Capillary Density Causing Tissue Anoxia
ANOXIC LETHAL CORNER
Blood Flow
paO2 150 mmHg
O2 RADIAL VECTORS
O2 AXIAL VECTORS
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3. METABOLIC ACIDOSIS Axial Kick Oxygen
Redistributed To The Lethal Corner
NO ANOXIC LETHAL CORNER
R
r
Blood Flow
paO2 500 mmHg
AUGMENTED O2 RADIAL VECTORS
AUGMENTED O2 AXIAL VECTORS
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3. METABOLIC ACIDOSIS
FiO2 50
FiO2 50
FiO2 52
FiO2 45
FiO2 46
FiO2 42
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3. METABOLIC ACIDOSISAxial Kick Keeps Potential
Lethal Corner Oxygenated
Potential 1 mmHg tissue pO2 line
Augmented O2 Axial Vectors
paO2 150 mmHg
Augmented O2 Radial Vectors
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3. METABOLIC ACIDOSIS Reduced Axial Kick Causes
Formation Of A Lethal Corner With Development Of
A Base Deficit
Reduced O2 Axial Vectors
1 mmHg tissue pO2 line
paO2 100 mmHg
Lethal Corner Forms Anoxic tissue
O2 Radial Vectors
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4. HYPOTHERMIC ARRESTProfound Hypothermic Bypass
And Circulatory ArrestThe Need for Dissolved
Oxygen

• Hemodilution reduces DO2
• Hypothermia alpha stat impairs O2 off loading
• Hyperoxia provides dissolved O2
• Dissolved oxygen satisfies most of the brain's
  oxygen requirements during profound hypothermic
  cardiopulmonary bypass.
• Dexter et al. 1997
• Used prior to DHCA normoxic CPB increases brain
  damage compared to hyperoxic CPB. The mechanism
  is hypoxic injury, which overwhelms any injury
  caused by oxygen free radicals.
• Nollert et al. 1999

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4. HYPOTHERMIC ARRESTBypass Hypothermia To
Oxygen Load Tissues
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4. HYPOTHERMIC ARRESTCirculatory Arrest
Extending The Safe Arrest Time
Adult Brain MET _at_ 18C 0.7 cc/kg/min
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4. HYPOTHERMIC ARREST Perfused Capillary Density
(PCD) alpha stat vs. pH stat
R
R
Low PCD Single capillary unit
High PCD Multiple capillary units
Open capillaries
Increasing PCD
Closed capillaries
pH stat 1. systemic vasodilation 2. increased
PCD 3. high CO2 (relative acidosis) 4.
oxyhemoglobin unloading promoted

• Alpha stat
• systemic vasoconstriction
• reduced PCD
• low CO2 (relative alkalosis)
• oxyhemoglobin unloading inhibited

High PCD and high CO2 enhances tissue oxygen
loading prior to deep hypothermic circulatory
arrest
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4. HYPOTHERMIC ARRESTAcid Produced During 60
Minutes Arrest _at_ 18?C
Normoxia pvO2 lt150 mmHg Hyperoxia pvO2 gt 300
mmHg
Pearl, Grist et al. 2000.
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Oxygen Toxicity vs Reperfusion Injury

• Oxygen toxicity
• normal capillary blood flow
• intracellular pH normal
• active antioxidants
• too much O2
• Reperfusion injury
• poor capillary blood flow
• intracellular pH change
• deactivated antioxidants
• reperfusion of capillaries tissues
• injury increases w/ O2 increase

AOX antioxidants ROS reactive oxygen species
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5. OXYGEN TOXICITYOff Gassing To Remove Nitrogen
From Microemboli In The BodyAnd Resetting The
Oxygen Clock

• Because of the effective defense systems
  (functioning antioxidants), the tolerance of
  viable human cells to (reactive oxygen species)
  is relatively high.
• Bauer Bauer. 1999
• USN uses 100 O2 to off gas N2 causing
  decompression sickness
• Oxygen toxicity prevented by five minute air
  breaks taken intermittently restore antioxidant
  reserve capacity
• Air breaks reduce CNS and pulmonary
  complications.
• U.S Navy Diving Manual. 1991

Take away lesson for perfusionists Reset the
oxygen clock and reduce the potential for cardiac
oxygen toxicity or reperfusion injury by reducing
FiO2 prior to cross clamp removal.
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5. OXYGEN TOXICITYNeurologic Complication
ComparisonCPB vs. Hyperbaric Hyperoxia

• CNS complications from CPB
• stroke 1.5 (CABG) to 10 (valves)
• asymptomatic brain infarct (MRI) 18
• Floyd et al. 2006
• Hyperbaric hyperoxia
• pO2 1520 mmHg (2 atm) to 2280 mmHg (3 atm) for
  1 to 10 hours decompression sickness, wound
  healing, infection, CO poisoning, radiation
  injury/necrosis, tissue grafts, burns
• CNS event lt 0.01
• Neumeister. 2008
• The risk of stroke is 150 - 1800 times greater
  during CPB than during hyperbaric hyperoxia

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6. REPERFUSION INJURYMyocyte Cell Death By
Ischemic Anoxia And Subsequent Reperfusion
(Reoxygenation)
21 O2 on for 3 hr 60 mortality
Experimental Group
O2 off for 1 hr 0 mortality
Control Group
O2 off for 4 hours 14 mortality
Becker. 2004
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6. REPERFUSION INJURYReperfusion Injury
Potential (RIP)Acronym for Rest In Peace

• RIP the hidden risk of a lethal reperfusion
  injury upon the sudden reperfusion of ischemic
  tissues, i.e., the presence of a lethal corner.
• Shock inadequate blood flow poor tissue
  oxygenation CO2 removal
• Cardiogenic
• Septic
• Traumatic
• Hypovolemic septic
• Neurogenic
• Shock a state of insufficient perfusion that
  holds the potential for reperfusion injury if
  normothermic oxygenation is suddenly restored.
• Low CPB flow at normothermia
• Transplanted organs

A cause of acute organ failure in transplants.
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6. REPERFUSION INJURYECPR Hemodilution/Hypothermi
a To Prevent Reperfusion Injury

• Capillaries damaged during reperfusion
• Reduced viscosity counters no reflow phenomenon
  (aka DIC)

• Patients develop RIP during resuscitation
• Hypothermia reduces O2 need
• Hemodilution reduces oxygen delivery to tissues
• Allows high blood flow without excessive O2
  delivery to facilitate CO2 removal.

www.benbest.com/cryonics/ischemia.html
Mouse lung after gastric ischemic/hypoxia
reperfusion
Normal mouse lung

• http//www.thoracic.org/sections/clinical-informat
  ion/critical-care/critical-care-research/animal-mo
  dels-of-acute-lung-injury.html

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6. Reperfusion InjuryPerfusionists need to
identify patients at risk for reperfusion injury
on CPB

• Hyperoxemic (paO2 400 mmHg) cardiopulmonary
  bypass did not produce oxidant damage or reduce
  functional recovery after cardiopulmonary bypass
  in non-hypoxemic controls.In contrast, abrupt
  and gradual reoxygenation (of pre-CPB hypoxemic
  subjects)...produced significant lipid
  peroxidation, lowered antioxidant reserve
  capacity and decreased functional recovery.
• Ihnken et al. 1995